3-AP in Treating Patients With Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00390052
First received: October 18, 2006
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

This phase I trial is studying the side effects and best dose of 3-AP in treating patients with advanced or metastatic solid tumors. 3-AP may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: triapine
Other: pharmacological study
Procedure: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum pharmacokinetics of oral triapine [ Time Frame: Baseline, day 4, and day 8 ] [ Designated as safety issue: No ]
    Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate. The relationship of the AUC to the dose will be assessed by least-square regression analysis.


Enrollment: 24
Study Start Date: December 2006
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients will receive a 2-hour infusion of 3-AP once in week 1. Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks. Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown.
Drug: triapine
Given IV and orally
Other Names:
  • 3-AP
  • OCX-191
Other: pharmacological study
correlative study
Other Name: pharmacological studies
Procedure: laboratory biomarker analysis
Correlative study

Detailed Description:

OBJECTIVES:

I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors.

II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients.

III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess tumoral expression of genes involved in response and resistance to 3-AP.

V. Observe and record any tumor response in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples for pharmacokinetic analysis are collected periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP during course 1.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Must be able to swallow
  • Histologically confirmed solid tumor
  • Advanced or metastatic disease
  • Measurable or evaluable disease
  • No known active CNS metastases
  • ECOG performance status 0-1
  • Life expectancy > 3 months
  • Progressive disease during >= 1 prior standard therapy OR disease unlikely to respond to any currently available therapies
  • Patients with previously treated CNS metastases who have no evidence of new CNS metastases AND are stable for >= 2 months are eligible
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 10 g/dL (transfusions allowed)
  • Absolute neutrophil count >= 1,500/mm^3
  • ALT and AST =< 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase =< 2.5 times ULN
  • Creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min
  • Bilirubin normal
  • PT/PTT =< 1.5 times ULN
  • FEV1 >= 1.2 L
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 2 weeks prior to and during study treatment
  • No mental deficits and/or psychiatric history that may preclude study treatment
  • No active heart disease, including any of the following: myocardial infarction within the past 3 months, symptomatic coronary artery disease or heart block, uncontrolled congestive heart failure
  • No moderate to severe compromise of pulmonary function
  • No active infection
  • No other life-threatening illness
  • No active coagulation disorder other than occult blood
  • No known positivity for glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Recovered from prior treatment
  • Prior gemcitabine allowed
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 3 weeks since prior radiotherapy or any other treatment for this cancer
  • No prior 3-AP
  • No concurrent radiotherapy
  • No other concurrent investigational agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390052

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Yun Yen Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00390052     History of Changes
Other Study ID Numbers: NCI-2009-00139, NCI-2009-00139, PHI-52, CDR0000507731, PHI-52, 7225, U01CA062505
Study First Received: October 18, 2006
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014